Schizophrenia susceptibility gene locus at Xp22.3

Multiple genetic loci have been implicated in the search for schizophrenia susceptibility genes, none having been proven as causal. Genetic heterogene ity is probable in the polygenic etiology of schizophrenia. We report on tw o unrelated Caucasian women with paranoid schizophrenia (meeting Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria) who have an Xp22.3 overlapping deletion characterized by fluorescence in situ hybridiza tion (FISH). Patient 1 was previously reported by us (Wyandt HE, Bugeau-Mic haud L, Skare JC, Milunsky A. Partial duplication of Xp: a case report and review of previously reported cases. Amer J Med Genet 1991 40. 280-283) to have a de novo partial duplication of Xp. At that time, she was a 24-year-o ld woman with short stature, irregular menses, other abnormalities suggesti ve of Turner syndrome, and paranoid schizophrenia. Recently, FISH analysis demonstrated that she has an inverted duplication (X)(p22.1p11.2) and a mic roscopic deletion (X)(p22.2p22.3) between DXS1233 and DXS7108 spanning appr oximately 16-18 cM. Patient 2 is a 14-year-old girl with short stature, lea rning disabilities, and paranoid schizophrenia. High-resolution chromosome analysis revealed a de novo deletion involving Xp22. FISH analysis showed t hat the deletion (X)(p22.2p22.3) spanned 10-12 cM between AFMB290XG5 and DX S1060. Given that deletions of Xp22 are not common events, the occurrence o f two unrelated schizophrenia patients with an overlapping deletion of this region would be extraordinarily rare. Hence, the deletion within Xp22.3 al most certainly contains a gene involved in the pathogenesis of paranoid sch izophrenia.